1. Field of the Invention
The present invention relates generally to systems and methods for assaying biological samples. More particularly, the present invention relates to a system and method for separating plasma from whole blood and transferring the plasma to an analytical substrate or device. The present invention also pertains to a system and method for dispensing whole or filtered blood and transferring dispensed blood to an analytical substrate or device.
Many diagnostic markers and other analytes are best determined from patient blood samples. The ability to measure such markers and analytes directly in blood, however, is problematic because of the presence of blood cells, particularly red blood cells, in whole blood. Thus, a majority of analytical systems and methods intended for measuring blood markers and analytes rely on detection in a plasma or serum sample, not in a whole blood sample.
A wide variety of blood separation systems and methods have been developed over the years particularly for use in performing plasma and serum assays. Such systems may be generally categorized as centrifugal, chemical, and filtration. Centrifugal systems rely on centrifugation to remove cellular components from the blood. Chemical systems rely on antibodies, lectins, or the like, for binding and removing cellular components. Finally, filtration relies on chromatographic and/or size-exclusion filtration elements for separating the cellular blood components from the resulting plasma fraction.
The present invention is concerned in particular with filtration systems and methods for producing plasma from whole blood prior to performing an assay on the plasma. Heretofore, filtration elements have often been constructed integrally in assay devices, where blood is applied to the filter element and plasma is separated and flows to a reaction zone. Such systems, however, generally require that the whole blood be initially transferred from the standard blood collection device, such as a syringe or more commonly a vacuum collection tube, often using a transfer pipette. The need to use a transfer pipette is disadvantageous in several respects. It increases the assay procedure time and introduces a source of contamination and error. Equally important, the need to remove blood from the collection device in an intermediate transfer step increases the likelihood of that personnel performing the assay will be exposed to the blood.
For these reasons, it would be desirable to provide improved systems and methods for separating plasma from whole blood for use in plasma assays and assay devices. It would be particularly desirable if such systems and methods could eliminate the need to employ an intermediate transfer step between the blood collection device and the blood filtration device, such as the use of a transfer pipette. It would be particularly desirable if the methods and devices would permit the direct separation of plasma from blood in a totally closed system, including the blood collection device, which could be disposed of after use without release of blood or blood components from the closed system (other than the plasma which has been intentionally transferred to an assay system). Such methods and systems should further provide for accurate and precise (repeatable) measurement of the plasma being separated, as well as for direct transfer of the plasma to a test substrate, receptacle, or other assay system.
Various systems and methods for dispensing blood and producing a measured amount of blood have also been developed over the years for use in performing blood assays. As with the plasma separation systems discussed above, systems and methods for dispensing blood typically require that the blood be initially transferred from a standard blood collection device, such as a syringe or vacuum collection tube, often using a transfer pipette. This transfer process is disadvantageous because it increases the assay procedure time and the possibility that personnel performing the assay will be exposed to the blood. Such process also introduces a source of contamination and error. It would thus be desirable to provide improved systems and methods for dispensing a measured volume of blood for use in blood assays and assay devices. It would be especially desirable if such systems and methods did not require an intermediate transfer step (e.g., as described above) to transfer blood from the collection device to the blood dispensing device. It would also be advantageous if such systems and methods would allow direct dispensation of blood from a totally closed system to protect against inadvertent release of the blood or bloods components. In addition, it would useful if such systems and methods would provide for precise measurement of the dispensed blood and direct transfer of dispensed blood to a test substrate or other assay device.
2. Description of the Background Art
U.S. Pat. No. 4,086,060, describes a blood filtering device which is employed between a blood collection device and a plasma receptacle. U.S. Pat. Nos. 4,980,297 and 4,970,052, describe plasma transfer devices which include needles for accessing blood collection devices and the rubber stoppers on the collection devices. The following patents describe other plasma separation systems and devices: U.S. Pat. Nos. 5,275,731; 5,262,049; 5,151,184; 4,957,637; 4,828,716; and 3,814,258. Filter elements for separating plasma from whole blood in combination with absorptive pads are shown in a number of patents, including U.S. Pat. Nos. 5,262,067; 5,132,086; 5,110,724; 4,987,085; 4,933,092; 4,816,224; 4,753,776; 4,477,575; and 3,663,374. Other patents showing assay devices including separation membranes and absorptive pads include U.S. Pat. Nos. 4,678,757; 4,952,516; 4,999,163; 5,000,922; 5,135,719; 5,186,843; 5,266,219; and 5,308,483.